{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:14:09Z","timestamp":1791861249921,"version":"4.3.4"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2011,5,17]],"date-time":"2011-05-17T00:00:00Z","timestamp":1305590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            A dynamic homeostasis is maintained between the host and native bacteria of the gastrointestinal tract in animals, but migration of bacteria from the gut to other organs can lead to disease or death.\n            <jats:named-content content-type=\"genus-species\">Enterococcus faecalis<\/jats:named-content>\n            is a commensal of the gastrointestinal tract; however,\n            <jats:italic>Enterococcus<\/jats:italic>\n            spp. are increasingly frequent causes of nosocomial infections with a high mortality rate. We investigated the commensal-to-pathogen switch undergone by\n            <jats:named-content content-type=\"genus-species\">E. faecalis<\/jats:named-content>\n            OG1RF in the lepidopteran model host\n            <jats:italic>Manduca sexta<\/jats:italic>\n            associated with its location in the host.\n            <jats:named-content content-type=\"genus-species\">E. faecalis<\/jats:named-content>\n            persists in the harsh midgut environment of\n            <jats:italic>M.\u00a0sexta<\/jats:italic>\n            larvae without causing apparent illness, but injection of\n            <jats:named-content content-type=\"genus-species\">E. faecalis<\/jats:named-content>\n            directly into the larval hemocoel is followed by rapid death. Additionally, oral ingestion of\n            <jats:named-content content-type=\"genus-species\">E. faecalis<\/jats:named-content>\n            in the presence of\n            <jats:named-content content-type=\"genus-species\">Bacillus thuringiensis<\/jats:named-content>\n            insecticidal toxin, a pore-forming toxin that targets the midgut epithelium, induces an elevated mortality rate. We show that the loss of gut integrity due to\n            <jats:named-content content-type=\"genus-species\">B. thuringiensis<\/jats:named-content>\n            toxin correlates with the translocation of\n            <jats:named-content content-type=\"genus-species\">E. faecalis<\/jats:named-content>\n            from the gastrointestinal tract into the hemolymph. Upon gaining access to the hemolymph,\n            <jats:named-content content-type=\"genus-species\">E. faecalis<\/jats:named-content>\n            induces an innate immune response, illustrated by hemocyte aggregation, in larvae prior to death. The degree of hemocyte aggregation is dependent upon the route of\n            <jats:named-content content-type=\"genus-species\">E. faecalis<\/jats:named-content>\n            entry. Our data demonstrate the efficacy of the\n            <jats:italic>M.\u00a0sexta<\/jats:italic>\n            larval model system in investigating\n            <jats:named-content content-type=\"genus-species\">E. faecalis<\/jats:named-content>\n            -induced sepsis and clarifies controversies in the field regarding the events leading to larval death following\n            <jats:named-content content-type=\"genus-species\">B. thuringiensis<\/jats:named-content>\n            toxin exposure.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            This study advances our knowledge of\n            <jats:named-content content-type=\"genus-species\">Enterococcus faecalis<\/jats:named-content>\n            -induced sepsis following translocation from the gut and provides a model for mammalian diseases in which the spatial distribution of bacteria determines disease outcomes. We demonstrate that\n            <jats:named-content content-type=\"genus-species\">E. faecalis<\/jats:named-content>\n            is a commensal in the gut of\n            <jats:italic>Manduca sexta<\/jats:italic>\n            and a pathogen in the hemocoel, resulting in a robust immune response and rapid death, a process we refer to as the \u201ccommensal-to-pathogen\u201d switch. While controversy remains regarding\n            <jats:named-content content-type=\"genus-species\">Bacillus thuringiensis<\/jats:named-content>\n            toxin-induced killing, our laboratory previously found that under some conditions, the midgut microbiota is essential for\n            <jats:named-content content-type=\"genus-species\">B. thuringiensis<\/jats:named-content>\n            toxin killing of\n            <jats:italic>Lymantria dispar<\/jats:italic>\n            (N. A. Broderick, K. F. Raffa, and J. Handelsman, Proc. Natl. Acad. Sci. U. S. A. 103:15196\u201315199, 2006; B. Raymond, et al., Environ. Microbiol. 11:2556\u20132563, 2009; P. R. Johnston, and N. Crickmore, Appl. Environ. Microbiol. 75:5094\u20135099, 2009). We and others have demonstrated that the role of the midgut microbiota in\n            <jats:named-content content-type=\"genus-species\">B. thuringiensis<\/jats:named-content>\n            toxin killing is dependent upon the lepidopteran species and formulation of\n            <jats:named-content content-type=\"genus-species\">B. thuringiensis<\/jats:named-content>\n            toxin (N. A. Broderick, K. F. Raffa, and J. Handelsman, Proc. Natl. Acad. Sci. U. S. A. 103:15196\u201315199, 2006; N. A. Broderick, et al., BMC Biol. 7:11, 2009). This work reconciles much of the apparently contradictory previous data and reveals that the\n            <jats:italic>M.\u00a0sexta-E.\u00a0faecalis<\/jats:italic>\n            system provides a model for mammalian sepsis.\n          <\/jats:p>","DOI":"10.1128\/mbio.00065-11","type":"journal-article","created":{"date-parts":[[2011,5,18]],"date-time":"2011-05-18T04:03:32Z","timestamp":1305691412000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":162,"title":["From Commensal to Pathogen: Translocation of Enterococcus faecalis from the Midgut to the Hemocoel of\n            <i>Manduca sexta<\/i>"],"prefix":"10.1128","volume":"2","author":[{"given":"Katie L.","family":"Mason","sequence":"first","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor A.","family":"Stepien","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessamina E.","family":"Blum","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan F.","family":"Holt","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA"},{"name":"Department of Bacteriology, University of Wisconsin, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Normand H.","family":"Labbe","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, University of Wisconsin, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S.","family":"Rush","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth F.","family":"Raffa","sequence":"additional","affiliation":[{"name":"Department of Entomology, University of Wisconsin, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo","family":"Handelsman","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.026385-0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/422002"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003093421007"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2006.01550.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/ee\/37.5.1344"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.0121.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.en.37.010192.003151"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00034-06"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-10-129"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.50.1.1-24.1986"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002849900310"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jee\/95.5.1018"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.42.2.385-387.1981"},{"key":"e_1_3_2_15_2","first-page":"152","article-title":"The site of action of crystalliferous bacteria in lepidoptera larvae","volume":"1","author":"Heimpel A","year":"1959","unstructured":"HeimpelA AngusT. 1959. 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